The clinical evaluation of an adverse reaction to food requires a careful history and physical examination to determine the type of adverse response, whether potentially IgE or non-IgE associated.2 Important factors to consider include the types of symptoms, the chronicity and reproducibility of the symptoms, and alternative explanations for symptoms. If symptoms indicate a nonimmune etiology, additional evaluation can be directed to the specific suspicion. For example, lactose intolerance may be confirmed by dietary elimination and challenge. For chronic disorders, such as atopic dermatitis and eosinophilic gastroenteritis, the identification of suspect foods is difficult, because food is ingested throughout the day and symptoms are often chronic with a waxing and waning course. Symptom diaries are helpful but rarely diagnostic. In addition, individuals with these disorders are often sensitized to multiple foods, many of which may not cause symptoms. Care in selecting and interpreting the tests is paramount, and consideration of the previously reviewed epidemiology and pathophysiology of food allergies is helpful for test selection and interpretation.
After a history is obtained, tests for food-specific IgE antibodies may be performed. The test modalities include skin prick tests, performed using a probe to introduce food protein to the superficial skin layer, or serum tests. The tests have similar performance characteristics. They are generally very sensitive (approximately 75%-95%) and modestly specific (approximately 30%-60%).2 Skin prick tests are used on rash-free skin when the patient is avoiding antihistamines; intradermal skin tests should not be used. Although commercial extracts are available for performing skin prick tests for many foods, fresh extracts, particularly when testing fruits and vegetables in which proteins are prone to degradation, may be more sensitive. If IgE antibody specific for the food protein is present, a wheal and flare will occur that is compared with positive (histamine) and negative (saline) controls. The skin prick test is available to allergists and has advantages of immediate results and low cost.
A more widely available test is a serum test for food-specific IgE antibodies. There are several commercial manufacturers of the test21; results among these tests are variable, probably because the reagents have slight differences in the proteins displayed. Previous generation tests used radioactivity (radioallergosorbent test), but these assays are no longer used. Like skin prick tests, serum IgE tests are generally composed of proteins extracted from the food being tested. However, immune responses to digestion-stable proteins are more likely to represent true allergies than those to heat- and digestion-labile food proteins. Tests have emerged to measure specific IgE against various component proteins in food. The best studied test is for peanut protein. IgE binding to the peanut protein Ara h 2, a stable protein, is associated with clinical allergy,22 and isolated IgE binding to Ara h 8, a labile pollen-related protein, is not generally associated with reactions. Component testing is commercially available for a limited number of foods, including milk (casein), egg (ovomucoid), and various tree nuts (Cor a1, 8, 9, and 14 for hazelnut; Ana o3 for cashew, Jug r 1 and 3 for walnut; Ber e1 for Brazil nut).
A positive skin prick test or serum IgE test result merely indicates that food-specific IgE is present, a state termed sensitization. Sensitization is not equivalent to a diagnosis of clinical allergy.1,2 Larger wheal diameters or increasing concentrations of IgE antibodies are associated with higher probability that the test reflects clinical allergy. The size of the wheal or the numerical value of IgE antibodies does not reflect severity of the allergic reaction. In a limited number of studies of a few foods in infants and children, diagnostic values associated with very high (≥95%) predictive values for reactions have been determined, although not universally confirmed.23
Food-specific IgE may be detected despite tolerance of a food or may remain detectable but typically declines as a food allergy resolves. Obtaining panels of food allergy tests without consideration of pertinent clinical history is not recommended because numerous irrelevant positive results may result, creating confusion and anxiety.1,2 Clinical history is key for test selection and interpretation. Food-specific IgE test results are expected to be negative when the pathophysiology of the response is consistent with non-IgE-mediated reactions. However, acute anaphylactic reactions may also occasionally occur despite a negative test result, so caution is needed when evaluating a patient with a convincing history but a negative test result. Neither the size of the skin prick test reaction nor concentration of IgE in serum usefully predicts the type or severity of reaction.
Other tests have been touted for the diagnosis of food allergy but have never been found useful in blinded studies. These tests, which are not recommended, include measurement of IgG4 antibody, provocation-neutralization (diluted liquid extracts of foods placed under the tongue or injected to diagnose and treat various symptoms), and applied kinesiology (muscle strength testing).2 A clinical report from the American Academy of Pediatrics (AAP) on the topic of allergy testing emphasized the benefits and limitations of the tests and provides additional recommendations as summarized in the text box.24
AAP Summary of IgE Test Characteristics and Limitations24
Treatment decisions for infants and children with allergy should be made on the basis of the appropriate diagnosis and identification of causative allergens, which may be identified through directed specific IgE testing.
Allergy tests for specific IgE must be selected and interpreted in the context of a clinical presentation; test relevance may vary according to the patient's age, allergen exposure, and performance characteristics of the test.
Positive specific IgE test results indicate sensitization, which is not equivalent to clinical allergy. Large panels of indiscriminately performed screening tests may, therefore, provide misleading information.
Tests for specific IgE may be influenced by cross-reactive proteins that may or may not have clinical relevance to disease.
Increasingly higher levels of specific IgE (higher concentrations on serum tests or skin prick test wheal size) generally correlate with an increased risk of clinical allergy.
Specific IgE test results typically do not reflect severity of allergies.
Tests for allergen-specific IgG antibodies are not helpful for diagnosing allergies.
Consultation with a board-certified allergist-immunologist should be considered, because test limitations often warrant additional evaluation to confirm the role of specific allergens.
For evaluation of chronic diseases such as atopic dermatitis and eosinophilic esophagitis, improvement of symptoms during dietary elimination of suspected foods provides presumptive evidence of causality. Elimination diets can be undertaken by removing foods suspected to be causing symptoms, removing all but a selected group of foods that are rarely allergenic (oligoantigenic diet), or giving an elemental diet consisting only of a hypoallergenic extensively hydrolyzed formula or a nonallergenic amino-acid-based formula. The elemental diet provides the most definitive trial but is difficult for children and teenagers to follow. The type of elimination diet selected will depend on a priori reasoning concerning offending foods on the basis of history and epidemiology, and, when appropriate, the results of tests for IgE antibody. The length of trial depends on the type of symptoms, but 1 to 6 weeks is usually the range required. Consultation with a dietitian may be needed to ensure nutritional sufficiency of trial diets. For breastfed infants, maternal dietary elimination is required. When a food to which IgE allergy has been demonstrated is removed from the diet during a chronic disorder, it is possible for reintroduction to induce severe reactions16,25; therefore, guidance from an allergist is prudent.
When history and IgE testing have not confirmed an allergy, or when the development of tolerance is suspected, an oral food challenge may be required to confirm clinical allergy.1,2 An oral food challenge is performed by feeding gradually increasing amounts of the suspected food under medical observation. 26 Oral food challenges are performed either openly, in which the patient and physician know the food being ingested, or blinded, by camouflaging the food in a carrier food. The double-blind placebo-controlled food challenge is least prone to bias and is considered the "gold standard." Briefly, this format of oral food challenge has a third party develop 2 food servings that are identical in taste and texture but in which only 1 contains the test allergen. The oral food challenge is randomized such that true or placebo doses are given, for example, on separate days, and the patient and observer are not aware of the content. The oral food challenge can be used to evaluate any type of adverse response. For non-IgE-mediated reactions, the oral food challenge is usually the only means of diagnosis. Feeding tests, particularly in IgE-mediated reactions and enterocolitis syndrome, can induce severe reactions. The supervising clinician, usually an allergist, must have medications and supplies for resuscitation immediately available to manage reactions. Negative challenges should always be followed by a supervised open feeding of an age-appropriate portion of the tested food in its commonly prepared state.